Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.
An obstacle to understanding neural mechanisms of movement is the complex, distributed nature of the mammalian motor system. Here we present a novel behavioral paradigm for high-throughput dissection of neural circuits underlying mouse forelimb control. Custom touch-sensing joysticks were used to quantify mouse forelimb trajectories with micron-millisecond spatiotemporal resolution. Joysticks were integrated into computer-controlled, rack-mountable home cages, enabling batches of mice to be trained in parallel. Closed loop behavioral analysis enabled online control of reward delivery for automated training. We used this system to show that mice can learn, with no human handling, a direction-specific hold-still center-out reach task in which a mouse first held its right forepaw still before reaching out to learned spatial targets. Stabilogram diffusion analysis of submillimeter-scale micromovements produced during the hold demonstrate that an active control process, akin to upright balance, was implemented to maintain forepaw stability. Trajectory decomposition methods, previously used in primates, were used to segment hundreds of thousands of forelimb trajectories into millions of constituent kinematic primitives. This system enables rapid dissection of neural circuits for controlling motion primitives from which forelimb sequences are built. NEW & NOTEWORTHY A novel joystick design resolves mouse forelimb kinematics with micron-millisecond precision. Home cage training is used to train mice in a hold-still center-out reach task. Analytical methods, previously used in primates, are used to decompose mouse forelimb trajectories into kinematic primitives.
BACKGROUND Pipeline embolization device (PED; Medtronic, Dublin, Ireland) utilization is not limited to the treatment of giant wide-necked aneurysms. It has been expanded to handle small blisters, fusiforms, and dissecting intracranial aneurysms. OBJECTIVE To report the use of the PED in various off-label distal cerebral circulation (DCC) arteries with a follow-up to assess clinical outcomes. METHODS Between 2011 and 2016, of 437 consecutive patients, 23 patients with aneurysms located in DCCs were treated with PED. Data on patient presentation, aneurysm characteristics, procedural outcomes, postoperative course, and aneurysm occlusion were gathered. To control confounding, we used multivariable logistic regression and propensity score conditioning. RESULTS A total of 437 patients (mean age 52.12 years; 62 women [14.2%]) underwent treatment with PED in our institution. Twenty-three of 437 (5.2%) received a pipeline in a distal artery: 11/23 middle cerebral artery, 6/23 posterior cerebral artery, 3/23 anterior cerebral artery (A1/A2, pericallosal artery), and 3/23 posterior inferior cerebellar artery. Twenty percent of the aneurysms were treated in the past, 10% had previously ruptured, and 5.9% ruptured at presentation to our hospital. The mean aneurysm size was 9.0 ± 6 mm. The mean follow-up was 12 mo (SD = 12.5). In multivariable logistic regression, no associations were found between PED deployment in DCCs and aneurysm occlusion or thromboembolic complications. PED use in DCC was associated with a good clinical outcome. Twenty-two people of 23 (95%) had a good clinical outcome in the latest follow-up. CONCLUSION Treatment of DCC aneurysms with PED is technically challenging mainly because of the small caliber and tortuosity of the parent arteries. The results of this study further support the safety of flow diverters in the treatment of various distal aneurysms.
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